Please Don't Call Me a Mutant.....

At our Tuesday Liver PowWow we also received confirmation of Peanut's Alagille status. Olivia is positive for 1 DNA Base Pair substitution at location 235 of the Jag1 Gene. Instead of a Cytosine nucleotide at that position, she has a Thymine nucleotide. Now think about this for 1 minute. There are 3 Billion total base pairs in the whole human genome, yet 1 lousy mistake/change has created ALL of Olivia's medical issues -- Heart, Liver & Kidneys.

What are the odds?:

• Winning a State Lotto 1 in 18 million
• Getting in a plane crash 1 in 11 million
• Getting struck by lighting in your lifetime 1 in 7000

Kind of changes your perspective on things eh? .....

Ok let's back up a bit and talk Genetics and DNA to understand exactly what is happening here. Our DNA is basically only made up of 4 different molecules :

• A -Adenine
• T - Thymine
• G - Guanine
• C - Cytosine

These Bases are strung together into

23 long 'strings' which are know as Chromosomes. Along the length of each Chromosome different segments are what we commonly call Genes. As we all know, Genes are what controls almost everything about us, Hair color, Eye color, Height, Brain development, Organ development, etc.

Each Base matches up with it's

corresponding partner and only that partner, creating Base Pairs and what we know as the Classic Double Helix of DNA.

• A with T
• G with C

These base pairs that make up our

DNA/Genes are basically the instructions on how to build and run our bodies. Each group of 3 base pairs codes for an Amino Acid which are the building blocks of proteins. Each gene when activated will then create sequence of Amino Acids which fold into a protein that has a specific function -- building cell walls, assembling more complex proteins, assembling hormones, etc.

The trick is that there are thousands of Genes on each continuous Chromosome, so there have to be certain areas that label the start and end of a certain Gene. These areas are referred to as Start and Stop Codons -- a collection of 3 bases in a specific order. This is where the Little O has her mutation. A normal Jag1 Gene consists of just over 36,000 base pairs, creating a protein of around 12,000 amino acids. Olivia's Jag1 gene has a T (Thymine) molecule where she should have a C (Cytosine) Molecule. This single base change in the gene creates a STOP Codon (TGA) at the 235th amino acid position where it should create a Arginine Amino Acid (CGA) . Basically this creates a significantly shortened/malformed Jagged1 Protein. This protein is critical in the development/migration of vessels within the growing fetus. If we then think about Heart, Liver and Kidneys --- all structures that rely heavily on vessel formation/migration --- we can see how those 3 organs get his hard by Alagille Syndrome (Jag1 Mutations).

From my understanding this mutation is one of the more common 'de novo' - or new mutations, at this locations. 60 to 70% these mutations are not inherited from either parent. At some point both Sara and I will get tested to see if we are carriers of this mutation and passed it on to Olivia, or if she just got Unlucky.....

I hope I didn't bore anyone too much with my basic genetic review, but I find it amazing and fascinating what an intricate machine we all are lucky enough to inhabit. Thank your lucky stars (or the deity of your choice) daily that your body was assembled correctly, the tiniest change at conception (or before) can have immeasurable consequences, and it's all due to the magic of DNA & Genes.